HIV-infected children in resource-limited settings do not reliably achieve the high levels of adherence to antiretroviral therapy (ART) seen in adults in the sanne setting and therefore represent a priority population for research. ART adherence assessment in children is complicated by limitations in self-report and absence of feasible objective measures. Moreover, existing adherence measures do not detect adherence lapses and offer opportunities to improve adherence before virologic failure. Novel adherence monitoring strategies are needed to better understand and intervene on pediatric ART adherence in resource-limited settings. In this five-year K23 career development award application, I propose to acquire the skills needed to address these issues and to achieve my long-term career goal of improving pediatric ART adherence and treatment outcomes in resource-limited settings. I have a good understanding of pediatric HIV/AIDS treatment and care through my prior work with the Clinton Foundation in China. I also have a master's degree in Health Services Research and am the principal investigator of an ongoing R21 study of multiple measures of ART adherence in Ugandan children. I, however, need a better understanding of quantitative analysis for adherence measures, novel adherence measurements, child development and mental health, and mixed- methods analysis to develop and test novel behavioral intervenfions to improve pediatric ART adherence. I have identified Dr. David Bangsberg as my primary mentor. He is an international expert in adherence research and has an outstanding track record of mentorship. Dr. Julius Kiwanuka and Dr. Steve Safren will serve as co-mentors in the areas of pediatric HIV/AIDS treatment and care and behavioral science, respectively. Using these skills, I propose to 1) examine the performance of novel adherence measures based on wireless technology among caregivers of HIV-infected children under age five in Uganda;2) perform mixed method assessments of the feasibility and acceptability of these novel adherence measures;and 3) develop a theoretic model for ART adherence behavior based on social capital for young children in a resource-limited setting. This model may be appropriate for young children, because their adherence largely reflects the behavior of their caregivers. The proposed training and mentorship will provide me with the skills and experience necessary to become a successful independent researcher. Toward the end of the award period, I will submit an ROI application to test an intervention based on wireless technology and the theoretic model that may improve adherence and viral suppression among HIV-infected Ugandan children. PUBLIC HEALTH RELEVANCE: Excellent adherence is essential for achieving and maintaining the clinical benefits of ART and for preventing virologic failure and drug resistance. Pediatric ART adherence in resource-limited settings is suboptimal and treatment is limited to a first-line regimen. The proposed research could significantly improve adherence, thus improving health and prolonging the use of first-line therapy. Moreover, it could improve the allocation of constrained resources by limiting expensive virologic testing to individuals with adherence failures.